Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER "wires" senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed -86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

中文翻译：

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8-氧鸟嘌呤DNA糖基化酶1驱动的DNA修复-肺衰老中的自相矛盾作用。

与年龄相关的肺部结构和功能变化是整体健康，认知活动和寿命的最重要预测指标。所有衰老细胞的共同点是氧化修饰的DNA碱基的增加，主要是8-oxo-7,8-dihydroguanine（8-oxoG）。它是通过由8-氧鸟嘌呤DNA糖基化酶1（OGG1-BER）驱动的DNA碱基切除修复途径修复的，该途径在衰老中的作用一直是许多研究的重点。这项研究假设，在细胞对OGG1-BER“导线”衰老/衰老过程的反应过程中，信号传导和随后的基因表达。为了测试OGG1-BER，是通过将二倍体肺成纤维细胞和小鼠气道反复暴露于8-oxoG碱基来模拟的。结果表明，反复接触会导致培养细胞的G1细胞周期停滞和成熟前衰老，其中有1000多个基因被差异表达-86％的基因与自然衰老的细胞相同。基因表达的基因本体分析显示，在培养的细胞和肺中，小GTP酶，磷酸肌醇3-激酶和有丝分裂原激活的激酶级联驱动了生物过程。这些结果共同指出了OGG1在衰老和与年龄相关的疾病过程中DNA损伤和修复作用的新范式。